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Background and objectivesAdiponectin (ADPN), an adipose tissue-derived hormone, has protective properties with respect to atherogenesis, inflammation, and energy homeostasis. Its beneficial role has not been consistent in patients with CKD or those undergoing dialysis.Design, setting, participants, & measurementsThis study examined the association of plasma ADPN levels in 987 prevalent kidney transplant recipients (mean age ± SD, 51.0±12.8 years; estimated GFR, 52.8±21.9 ml/min per 1.73 m(2); median time since transplant, 78 months) on all-cause mortality and death-censored graft failure. Patients were enrolled between February and August 2007 and were followed for a median of 51 months (interquartile range, 49-53 months). Using Cox proportional hazard models, the association of log-transformed plasma adiponectin was studied, with and without adjustment for demographic variables, baseline GFR, markers of inflammation, and cardiovascular risk factors.ResultsAt baseline, patients in the lowest ADPN tertile were significantly more likely to be male; to be smokers; to have a higher baseline GFR, lower systolic BP, and lower HDL cholesterol level; and to have higher body mass index, abdominal circumference, C-reactive protein level, and total cholesterol level. The adjusted hazard ratio for death with elevated plasma ADPN (per natural log) was 1.44, and there was no significant interaction with any relevant cardiovascular risk subgroups (i.e., advanced age; diabetes; or elevated body mass index, waist circumference, C-reactive protein, or Framingham risk score). The hazard for death-censored graft failure was nonsignificant at 1.03.ConclusionElevated ADPN levels are associated with higher risk for death but not allograft failure in prevalent kidney transplant recipients.

Background and objectivesAdiponectin (ADPN), an adipose tissue-derived hormone, has protective properties with respect to atherogenesis, inflammation, and energy homeostasis. Its beneficial role has not been consistent in patients with CKD or those undergoing dialysis.Design, setting, participants, & measurementsThis study examined the association of plasma ADPN levels in 987 prevalent kidney transplant recipients (mean age ± SD, 51.0±12.8 years; estimated GFR, 52.8±21.9 ml/min per 1.73 m(2); median time since transplant, 78 months) on all-cause mortality and death-censored graft failure. Patients were enrolled between February and August 2007 and were followed for a median of 51 months (interquartile range, 49-53 months). Using Cox proportional hazard models, the association of log-transformed plasma adiponectin was studied, with and without adjustment for demographic variables, baseline GFR, markers of inflammation, and cardiovascular risk factors.ResultsAt baseline, patients in the lowest ADPN tertile were significantly more likely to be male; to be smokers; to have a higher baseline GFR, lower systolic BP, and lower HDL cholesterol level; and to have higher body mass index, abdominal circumference, C-reactive protein level, and total cholesterol level. The adjusted hazard ratio for death with elevated plasma ADPN (per natural log) was 1.44, and there was no significant interaction with any relevant cardiovascular risk subgroups (i.e., advanced age; diabetes; or elevated body mass index, waist circumference, C-reactive protein, or Framingham risk score). The hazard for death-censored graft failure was nonsignificant at 1.03.ConclusionElevated ADPN levels are associated with higher risk for death but not allograft failure in prevalent kidney transplant recipients.

BackgroundDelayed graft function (DGF) complicates kidney allograft outcomes in the immediate post-transplantation period. We hypothesized that in hemodialysis patients more severe anemia, iron deficiency, the requirement for higher doses of erythropoietin-stimulating agents (ESA), or blood transfusions prior to transplantation are associated with higher risk of DGF.MethodsLinking five-yr hemodialysis patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 11 836 hemodialysis patients. Using logistic regression analyses we examined the association between pre-transplant parameters and post-transplant DGF.ResultsPatients were 49 ± 14 (mean ± SD) yr old and included 38% women, 27% blacks, and 26% diabetics. After adjusting for relevant covariates, pre-transplant blood transfusion was associated with 33% higher DGF risk (odds ratio [OR] = 1.33; 95% confidence interval [CI]: 1.19-1.48); and each 5000 U/wk increase of pre-transplant ESA dose with 5% higher DGF (OR = 1.05; 95% CI: 1.02-1.09). Compared to pre-transplant blood hemoglobin of 12-12.99 g/dL, there was 25% higher risk of DGF with blood hemoglobin 10-10.99 g/dL (OR = 1.25; 95% CI: 1.01-1.55), whereas blood hemoglobin ≥13 g/dL exhibited 15% higher risk of DGF (OR = 1.15; 95% CI: 0.98-1.34).ConclusionsPre-transplant blood transfusion, higher ESA dose, and either high or low blood hemoglobin but not iron markers are associated with higher risk of DGF.

BackgroundRacial and ethnic disparities among North American patients with chronic kidney disease have received significant attention. In contrast, little is known about health-related outcomes of patients with end-stage renal disease among the Roma minority, also known as gypsies, compared to Caucasian individuals. We prospectively assessed the association between Roma ethnicity and long-term clinical outcomes in kidney transplant recipients.MethodsIn a prevalent cohort of renal transplant recipients, followed up over a median of 94 months, we prospectively collected socio-demographic, medical (and transplant related) characteristics and laboratory data at baseline from 60 Roma and 1,003 Caucasian patients (mean age 45 (SD = 11) and 49 (SD = 13) years, 33 and 41% women, 18 and 17% with diabetes mellitus, respectively). Survival analyses examined the associations between Roma ethnicity and all-cause mortality and death-censored graft loss or death with functioning renal allograft.ResultsDuring the follow-up period, 341 patients (32%) died. Two-hundred eighty (26%) patients died with a functioning graft and 201 patients (19%) returned to dialysis. After multivariable adjustments, Roma ethnicity was associated with 77% higher risk of all-cause mortality (Hazard Ratio (HR): 1.77; 95% confidence interval (CI): 1.02, 3.07), two times higher risk of mortality with functioning graft (2.04 [1.17-3.55]) and 77% higher risk of graft loss (1.77 [1.01-3.13]), respectively.ConclusionsRoma ethnicity is independently associated with increased mortality risk and worse graft outcome in kidney transplant recipients. Further studies should identify the factors contributing to worse outcomes among Roma patients.

BackgroundRacial and ethnic disparities among North American patients with chronic kidney disease have received significant attention. In contrast, little is known about health-related outcomes of patients with end-stage renal disease among the Roma minority, also known as gypsies, compared to Caucasian individuals. We prospectively assessed the association between Roma ethnicity and long-term clinical outcomes in kidney transplant recipients.MethodsIn a prevalent cohort of renal transplant recipients, followed up over a median of 94 months, we prospectively collected socio-demographic, medical (and transplant related) characteristics and laboratory data at baseline from 60 Roma and 1,003 Caucasian patients (mean age 45 (SD = 11) and 49 (SD = 13) years, 33 and 41% women, 18 and 17% with diabetes mellitus, respectively). Survival analyses examined the associations between Roma ethnicity and all-cause mortality and death-censored graft loss or death with functioning renal allograft.ResultsDuring the follow-up period, 341 patients (32%) died. Two-hundred eighty (26%) patients died with a functioning graft and 201 patients (19%) returned to dialysis. After multivariable adjustments, Roma ethnicity was associated with 77% higher risk of all-cause mortality (Hazard Ratio (HR): 1.77; 95% confidence interval (CI): 1.02, 3.07), two times higher risk of mortality with functioning graft (2.04 [1.17-3.55]) and 77% higher risk of graft loss (1.77 [1.01-3.13]), respectively.ConclusionsRoma ethnicity is independently associated with increased mortality risk and worse graft outcome in kidney transplant recipients. Further studies should identify the factors contributing to worse outcomes among Roma patients.

BackgroundDelayed graft function (DGF) complicates kidney allograft outcomes in the immediate post-transplantation period. We hypothesized that in hemodialysis patients more severe anemia, iron deficiency, the requirement for higher doses of erythropoietin-stimulating agents (ESA), or blood transfusions prior to transplantation are associated with higher risk of DGF.MethodsLinking five-yr hemodialysis patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 11 836 hemodialysis patients. Using logistic regression analyses we examined the association between pre-transplant parameters and post-transplant DGF.ResultsPatients were 49 ± 14 (mean ± SD) yr old and included 38% women, 27% blacks, and 26% diabetics. After adjusting for relevant covariates, pre-transplant blood transfusion was associated with 33% higher DGF risk (odds ratio [OR] = 1.33; 95% confidence interval [CI]: 1.19-1.48); and each 5000 U/wk increase of pre-transplant ESA dose with 5% higher DGF (OR = 1.05; 95% CI: 1.02-1.09). Compared to pre-transplant blood hemoglobin of 12-12.99 g/dL, there was 25% higher risk of DGF with blood hemoglobin 10-10.99 g/dL (OR = 1.25; 95% CI: 1.01-1.55), whereas blood hemoglobin ≥13 g/dL exhibited 15% higher risk of DGF (OR = 1.15; 95% CI: 0.98-1.34).ConclusionsPre-transplant blood transfusion, higher ESA dose, and either high or low blood hemoglobin but not iron markers are associated with higher risk of DGF.

Intravenously infused liposomes may induce cardiopulmonary distress in some human subjects, which is a manifestation of “complement activation-related pseudoallergy.” We have now examined liposome-mediated complement activation in human sera with elevated lipoprotein (LDL and HDL) levels, since abnormal or racial differences in serum lipid profiles seem to modulate the extent of complement activation and associated adverse responses. In accordance with our earlier observations, cholesterol-rich (45 mol% cholesterol) liposomes activated human complement, as reflected by a significant rise in serum level of S-protein-bound form of the terminal complex (SC5b-9). However, liposome-induced rise of SC5b-9 was significantly suppressed when serum HDL cholesterol levels increased by 30%. Increase of serum LDL to levels similar to that observed in heterozygous familial hypercholesterolemia also suppressed liposome-mediated SC5b-9 generation considerably. While intravenous injection of cholesterol-rich liposomes into pigs was associated with an immediate circulatory collapse, the drop in systemic arterial pressure following injection of liposomes preincubated with human lipoproteins was slow and extended. Therefore, surface-associated lipoprotein particles (or apolipoproteins) seem to lessen liposome-induced adverse haemodynamic changes, possibly as a consequence of suppressed complement activation in vivo. PEGylated liposomes were also capable of activating the human complement system, and the presence of surface projected methoxypoly(ethylene glycol) chains did not interfere with generation of C3 opsonic fragments. We also show that poly(ethylene glycol) is not responsible for PEGylated liposome-mediated complement activation. The net anionic charge on the phosphate moiety of the phospholipid-mPEG conjugate seemed to play a critical role in activation of both the classical and alternative pathways of the complement system.